Conditional in vivo deletion of LYN kinase has little effect on a BRCA1 loss-of-function-associated mammary tumour model

Tornillo, Giusy, Warrington, Lauren, Kendrick, Howard, Higgins, Adam T. ORCID: https://orcid.org/0000-0002-2906-8151, Hay, Trevor, Beck, Sam and Smalley, Matthew J. ORCID: https://orcid.org/0000-0001-9540-1146 2024. Conditional in vivo deletion of LYN kinase has little effect on a BRCA1 loss-of-function-associated mammary tumour model. Disease Models and Mechanisms 17 (1) , dmm050211. 10.1242/dmm.050211

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Abstract

LYN kinase is expressed in BRCA1 loss-of-function-dependent mouse mammary tumours, in the cells of origin of such tumours, and in human breast cancer. Suppressing LYN kinase activity in BRCA1-defective cell lines, as well as in in vitro cultures of Brca1-null mouse mammary tumours, is deleterious to their growth. Here, we have examined the interaction between LYN kinase and BRCA1 loss-of-function in an in vivo mouse mammary tumour model, using conditional knockout Brca1 and Lyn alleles. Comparison of Brca1 tumour cohorts showed little difference in mammary tumour formation between animals that were wild type, heterozygous or homozygous for the conditional Lyn allele, although this was confounded by factors including incomplete Lyn recombination in some tumours. RNAseq analysis demonstrated that tumours with high levels of Lyn gene expression had a slower doubling time, but this was not correlated with levels of LYN staining in tumour cells themselves. Rather, high Lyn expression and slower tumour growth were likely a result of Bcell infiltration. The multifaceted role of LYN means it is likely to present difficulties as a therapeutic target in breast cancer.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences European Cancer Stem Cell Research Institute (ECSCRI)
Publisher:	The Company of Biologists
ISSN:	1754-8403
Date of First Compliant Deposit:	18 December 2023
Date of Acceptance:	15 December 2023
Last Modified:	25 Jan 2024 12:20
URI:	https://orca.cardiff.ac.uk/id/eprint/164881

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